System and method for metabolic mr imaging of a hyperpolarized agent

ABSTRACT

A system and method for metabolic MR imaging of a hyperpolarized agent includes exciting a single metabolic species of a hyperpolarized agent injected into a subject of interest. MR signals are acquired from the excited single metabolic species and an image is reconstructed from the acquired MR signals.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a continuation of and claims priority to U.S.patent application Ser. No. 11/623,277 filed Jan. 15, 2007, thedisclosure of which is incorporated herein.

BACKGROUND OF THE INVENTION

The present invention relates generally to MR imaging and, moreparticularly, to metabolic MR imaging of a hyperpolarized agent.

When a substance such as human tissue is subjected to a uniform magneticfield (polarizing field B₀), the individual magnetic moments of thespins in the tissue attempt to align with this polarizing field, butprecess about it in random order at their characteristic Larmorfrequency. If the substance, or tissue, is subjected to a magnetic field(excitation field B₁) which is in the x-y plane and which frequency isnear the Larmor frequency, the net aligned moment, or “longitudinalmagnetization”, M_(Z), may be rotated, or “tipped”, into the x-y planeto produce a net transverse magnetic moment M_(t). A signal is generatedby the excited spins after the excitation signal B₁ is terminated andthis signal may be received and processed to form an image.

When utilizing these signals to produce images, magnetic field gradients(G_(x), G_(y), and G_(z)) are employed. Typically, the region to beimaged is scanned by a sequence of measurement cycles in which thesegradients vary according to the particular localization method beingused. The resulting set of received NMR signals are digitized andprocessed to reconstruct the image using one of many well knownreconstruction techniques. It is desirable that the imaging process,from data acquisition to reconstruction, be performed as quickly aspossible for improved patient comfort and throughput.

For some procedures and investigations, it is also desirable for MRimages to display spectral information in addition to spatialinformation. One known method for acquiring MR signals andreconstructing MR images containing both spatial and spectralinformation is “chemical shift imaging” (CSI). CSI has been employed tomonitor metabolic and other internal processes of patients, includingimaging hyperpolarized substances such as ¹³C labeled contrast agentsand metabolites thereof. However, after injection of the hyperpolarizedagent, imaging is a challenging task. The hyperpolarization of the agenthas a limited lifetime, and imaging must be done rapidly. For example,typical T1 lifetimes of hyperpolarized agents are on the order of a fewminutes in vivo. Furthermore, the RF excitations of the pulse sequencemay destroy the hyperpolarization irreversibly.

The CSI method has some drawbacks which limit available signal-to-noiseratio, and thus image quality. For example, CSI tends to acquire dataslowly, considering the short lifetimes of the increased magnetizationof hyperpolarized substances. In addition, CSI typically exposes theimaging subject to a large number of RF excitations. These propertiesare especially unfavorable for a hyperpolarized agent because thehyperpolarized agent magnetization has a limited lifetime and isdestroyed by the RF excitations of the CSI sequence. As a consequence,the available magnetization cannot be fully utilized by the CSI method,and the signal-to-noise ratio (SNR) is thus reduced.

Additionally, MR procedures which require very fast, or periodic dataacquisition, such as cardiac imaging or metabolic imaging of the heart,are difficult to perform with CSI sequences because CSI can take morethan 15 seconds for a 16×16 matrix, whereas cardiac and relatedmetabolic imaging should be completed within a few heartbeats or a fewseconds.

It would therefore be desirable to have a system and method capable ofexciting and imaging a metabolic species of a hyperpolarized agentwithout affecting magnetization of metabolic species at otherfrequencies.

BRIEF DESCRIPTION OF THE INVENTION

Embodiments of the present invention provide a system and method of MRthat overcome the aforementioned drawbacks. A single metabolic speciesof a hyperpolarized agent injected into a subject of interest isexcited, and MR signals from the excited single metabolic species areacquired. An image is reconstructed from the acquired MR signals.

Therefore, in accordance with one aspect of the present invention, anMRI apparatus includes an MRI assembly having a plurality of gradientcoils positioned about a bore of a magnet to impress a polarizingmagnetic field. An RF transceiver system and an RF switch are controlledby a pulse module to transmit and receive RF signals to and from an RFcoil assembly to acquire MR images. The MRI apparatus also includes asystem controller coupled to the MRI assembly, the system controllerconfigured to cause the RF coil assembly to excite a single metabolicspecies of a hyperpolarized agent injected into a subject of interest.The system controller further causes the RF transceiver system toacquire MR signals from the excited single metabolic species andreconstruct an image from the acquired MR signals.

In accordance with another aspect of the invention, a method ofhyperpolarized agent MR imaging includes injecting a hyperpolarizedagent into a subject of interest and exciting a first metabolic speciesof the hyperpolarized agent. The method also includes acquiring MRsignals from the excited first metabolic species and reconstructing animage from the acquired MR signals.

According to a further embodiment of the invention, a computer readablestorage medium includes a computer program stored thereon comprisinginstructions which when executed by a computer, causes the computer tomodulate a plurality of flip angle train RF pulses of a pulse sequence.The instructions further cause the computer to acquire MR data from theplurality of molecules and generate an image from the MR data.

Various other features and advantages will be made apparent from thefollowing detailed description and the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate embodiments presently contemplated for carryingout the invention.

In the drawings:

FIG. 1 is a schematic block diagram of an MR imaging system for use withembodiments of the present invention.

FIG. 2 is a pulse sequence diagram of a trueFISP sequence with the slicegradient omitted.

FIG. 3 is a graph of the signal of the trueFISP sequence of FIG. 2 as afunction of phase accumulation between two successive RF pulses with aconstant flip angle of 90°.

FIG. 4 is a graph of the signal of the trueFISP sequence of FIG. 2 as afunction of phase accumulation between two successive RF pulses with aconstant flip angle of 1°.

FIG. 5 is a graph of the longitudinal magnetization of the trueFISPsequence of FIG. 2 as a function of phase accumulation between twosuccessive RF pulses with a constant flip angle of 1°.

FIG. 6 is a modulation envelope of an RF pulse amplitude in accordancewith an embodiment of the present invention.

FIG. 7 is a graph of trueFISP signals from hyperpolarized spins asfunction of phase shift per TR and RF pulse number.

FIG. 8 is another modulation envelope of the RF pulse amplitude inaccordance with an embodiment of the present invention.

FIG. 9 is a pulse sequence diagram incorporating the pulse sequencemodulation envelope of FIG. 8 in accordance with an embodiment of thepresent invention.

FIG. 10 is another modulation envelope of the RF pulse amplitude inaccordance with an embodiment of the present invention.

FIG. 11 is a pulse sequence diagram incorporating the pulse sequencemodulation envelope of FIG. 10 in accordance with an embodiment of thepresent invention.

FIG. 12 is a graph of frequency selectivity of a trueFISP sequenceincorporating a constant amplitude of the RF pulses in accordance withan embodiment of the present invention.

FIG. 13 is a graph of frequency selectivity of a trueFISP sequenceincorporating a Gaussian modulation envelope of the RF pulse amplitudein accordance with an embodiment of the present invention.

FIG. 14 is a graph of frequency selectivity of a trueFISP sequenceincorporating a sinc modulation envelope of the RF pulse amplitude inaccordance with an embodiment of the present invention.

FIG. 15 is a flowchart setting forth the steps of a technique inaccordance with an embodiment of the present invention.

FIG. 16 is an exemplary image acquired in accordance with an embodimentof the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIG. 1, the major components of a preferred magneticresonance imaging (MRI) system 10 that may incorporate embodiments ofthe present invention are shown. The operation of the system iscontrolled from an operator console 12 which includes a keyboard orother input device 13, a control panel 14, and a display screen 16. Theconsole 12 communicates through a link 18 with a separate computersystem 20 that enables an operator to control the production and displayof images on the display screen 16. The computer system 20 includes anumber of modules which communicate with each other through a backplane20 a. These include an image processor module 22, a CPU module 24 and amemory module 26, known in the art as a frame buffer for storing imagedata arrays. The computer system 20 is linked to disk storage 28 andremovable storage 30 for storage of image data and programs, andcommunicates with a separate system control 32 through a high speedserial link 34. The input device 13 can include a mouse, joystick,keyboard, track ball, touch activated screen, light wand, voice control,or any similar or equivalent input device, and may be used forinteractive geometry prescription.

The system control 32 includes a set of modules connected together by abackplane 32 a. These include a CPU module 36 and a pulse generatormodule 38 which connects to the operator console 12 through a seriallink 40. It is through link 40 that the system control 32 receivescommands from the operator to indicate the scan sequence that is to beperformed. The pulse generator module 38 operates the system componentsto carry out the desired scan sequence and produces data which indicatesthe timing, strength and shape of the RF pulses produced, and the timingand length of the data acquisition window. The pulse generator module 38connects to a set of gradient amplifiers 42, to indicate the timing andshape of the gradient pulses that are produced during the scan. Thepulse generator module 38 can also receive patient data from aphysiological acquisition controller 44 that receives signals from anumber of different sensors connected to the patient, such as ECGsignals from electrodes attached to the patient. And finally, the pulsegenerator module 38 connects to a scan room interface circuit 46 whichreceives signals from various sensors associated with the condition ofthe patient and the magnet system. It is also through the scan roominterface circuit 46 that a patient positioning system 48 receivescommands to move the patient to the desired position for the scan.

The gradient waveforms produced by the pulse generator module 38 areapplied to the gradient amplifier system 42 having Gx, Gy, and Gzamplifiers. Each gradient amplifier excites a corresponding physicalgradient coil in a gradient coil assembly generally designated 50 toproduce the magnetic field gradients used for spatially encodingacquired signals. The gradient coil assembly 50 forms part of a magnetassembly 52 which includes a polarizing magnet 54 and a whole-body RFcoil 56. A transceiver module 58 in the system control 32 producespulses which are amplified by an RF amplifier 60 and coupled to the RFcoil 56 by a transmit/receive switch 62. The resulting signals emittedby the excited nuclei in the patient may be sensed by the same RF coil56 and coupled through the transmit/receive switch 62 to a preamplifier64. The amplified MR signals are demodulated, filtered, and digitized inthe receiver section of the transceiver 58. The transmit/receive switch62 is controlled by a signal from the pulse generator module 38 toelectrically connect the RF amplifier 60 to the coil 56 during thetransmit mode and to connect the preamplifier 64 to the coil 56 duringthe receive mode. The transmit/receive switch 62 can also enable aseparate RF coil (for example, a surface coil) to be used in eithertransmit or receive mode.

The MR signals picked up by the RF coil 56 are digitized by thetransceiver module 58 and transferred to a memory module 66 in thesystem control 32. A scan is complete when an array of raw k-space datahas been acquired in the memory module 66. This raw k-space data isrearranged into separate k-space data arrays for each image to bereconstructed, and each of these is input to an array processor 68 whichoperates to Fourier transform the data into an array of image data. Thisimage data is conveyed through the serial link 34 to the computer system20 where it is stored in memory, such as disk storage 28. In response tocommands received from the operator console 12, this image data may bearchived in long term storage, such as on the removable storage 30, orit may be further processed by the image processor 22 and conveyed tothe operator console 12 and presented on the display 16.

A true fast imaging with steady presession (trueFISP) pulse sequencehaving low flip angles is described herein. As used herein, low flipangles are flip angles less than 15°. As described below, using low flipangles in conjunction with a trueFISP pulse sequence allows excitationand MR data acquisition of a single metabolite of a hyperpolarizedagent, such as ¹³C, while minimizing adverse effects on themagnetization of other metabolites. As such, the full magnetization ofthe hyperpolarized agent can be used for image generation. That is, insteady-state proton imaging, the relatively short relaxation times ofprotons make the signal to be approximately 25% of M₀. In contrast, themuch longer relaxation times of ¹³C makes it possible to reach atransient response with a maximum signal close to 100% of M₀ as shownbelow.

FIG. 2 shows a pulse sequence diagram of a trueFISP sequence 70according to one embodiment of the present invention. The trueFISPsequence 70 is a fully balanced steady-state free precession (SSFP)sequence. TrueFISP sequence 70 includes balanced gradients 72 in theread or frequency direction and balanced gradients 74 in the phasedirection applied between RF pulses 76, 78. During read gradient 80, asignal 82 is acquired, filling one k-space line.

The trueFISP pulse sequence 70 is characterized by the signal 82 beingdependent on a phase accumulation of the spins during the TR interval,i.e., the time between successive RF excitations. For spins perfectly onresonance, this phase accumulation is zero, but will be non-zero foroff-resonance spins. As shown in FIG. 3, for a trueFISP pulse sequencewith 90° flip angles of thermal equilibrium spins at steady-state,maximum signals 84 are obtained when the phase accumulation is ±2n·π(n=0, 1, 2 . . . ), and minimum signals 86 are obtained when the phaseaccumulation is π±2n·π (n=0, 1, 2 . . . ). In reconstructed trueFISPimages, the signal minima are visible as dark stripes. The off-resonancemay be caused by inhomogeneities of the B0 field, or chemical shift.

However, as shown in FIG. 4, if the flip angles of the trueFISP sequence70 (shown in FIG. 2) are set to a low flip angle, e.g., 1°, an oppositeresult to that of FIG. 3 is obtained. Setting the flip angle to 1°results in obtaining maximum signals 88 when the phase accumulation isπ±2n·π (n=0, 1, 2 . . . ), and obtaining minimum signals 90 when thephase accumulation is ±2n·π (n=0, 1, 2 . . . ). Accordingly, signals 88are obtained from a range of phase shifts at the same positions wheresignal minima were found for the signals shown in FIG. 3.

FIG. 5 shows the longitudinal magnetization 92 (Mz) for the trueFISPsequence 70 (shown in FIG. 2) set to a low flip angle of 1°. Thelongitudinal magnetization 92 is minimally affected outside excitationbands 94. Consequently, magnetization from other metabolites will bepreserved in an application with hyperpolarized substances. The positionof the excitation bands 94 can be moved from phase=±π to an arbitraryposition by changing the phase cycling of the RF pulse. The width of theexcitation profile is approximately 0.15° phase accumulation for a 1°flip angle. If TR=2 ms, a phase accumulation of 0.15° translates to aspectral width of approximately 12 Hz, or 0.75 ppm, for ¹³C at 1.5 T.The width of the excitation profile may also be modified by changing theflip angle.

FIG. 6 shows an RF pulse amplitude modulation envelope 96 according toone embodiment of the present invention. RF pulse amplitude modulationenvelope 96 is a constant modulation envelope to which flip angles ofthe trueFISP sequence 70 (shown in FIG. 2) are set to acquire thesignals of FIG. 4. As discussed above with regard to FIG. 4 and as shownin FIG. 6, the flip angles of the trueFISP sequence 70 (shown in FIG. 2)may be set to a constant, low flip angle, such as 1°, with total flipangle ranging from 90° to 180°. However, it is contemplated that the lowflip angle may be greater or lesser than 1°.

The behavior of hyperpolarized spins differs from that of spins atthermal equilibrium. After a transient phase, thermal equilibrium spinswill reach a steady-state, where the signal (the transversemagnetization) levels out at typically 20%-50% of M₀. However, when thespins are hyperpolarized and the relaxation times are long compared withthe duration of the scan, no steady-state is reached. Rather, themagnetization will gradually be tilted by the RF pulses from a startingposition along the z-axis down to the xy-plane.

FIG. 7 shows trueFISP signals 98 from hyperpolarized spins as functionof phase shift per TR and RF pulse number. The trueFISP signals 98 wereacquired using a flip angle of 1°, and the magnetization is aligned withthe z-axis before the first pulse. Further, the trueFISP signals 98 wereacquired with TR=2.5 ms, T₁=30 s, and T₂=2 s. It can be seen thatmaximum signals 100, i.e., after the 90th RF pulse, equals M₀. Thus, thefull hyperpolarized signal can be utilized, despite the low flip angle.

FIG. 8 shows a pulse sequence modulation envelope 102 according toanother embodiment of the present invention. Pulse sequence modulationenvelope 102 is a Gaussian-shaped modulation envelope to which flipangles of the trueFISP sequence 70 (shown in FIG. 2) may be set suchthat the total flip angle ranges from 90° to 180°. In a preferredembodiment, maximum pulse 105 has a flip angle between 5° and 15°.

FIG. 9 shows a pulse sequence according to the pulse sequence modulationenvelope 102 of FIG. 8. RF pulses 104 are modulated according to theGaussian-shaped modulation envelope 102, and phase gradient pulses 106,read gradient pulses 108, and slice encoding gradient pulses 110 arealso determined.

In addition to the Gaussian-shaped modulation envelope 102 shown in FIG.8, it is contemplated that other modulation envelope shapes arepossible. For example, FIG. 10 shows an RF pulse modulation envelope 112having a shape of a sinc function. FIG. 11 shows a pulse sequenceaccording to the pulse sequence modulation envelope 112 of FIG. 10. RFpulses 113 are modulated according to the shape of the sinc functionmodulation envelope 112 such that the total flip angle ranges from 90°to 180°. In a preferred embodiment, maximum pulse 114 has a flip anglebetween 5° and 15°.

FIGS. 12-14 show frequency selectivity of trueFISP sequences havingdifferent amplitude modulations of the RF flip angle. The signals 115,116, 118 shown in FIGS. 12-14, respectively, have been calculated for arepetition time (TR) of 2.5 ms, which is assumed to represent about theshortest possible TR for ¹³C imaging on a high-end clinical MR scanner.If the TR can be shortened further, the excitation for FIGS. 12-14 willcover a broader frequency range. Furthermore, calculations were made fora sequence with 96 phase-encoding steps and a total flip angle of 120°.The signal responses shown in FIGS. 12-14 are shown after 48 RF pulses,i.e., at the center of the k-space, with a linear phase-encoding scheme.

FIG. 12 shows that, with constant RF amplitude at a flip angle of 1.3°,the usable frequency range for a reasonably uniform signal intensity isapproximately 5 Hz, or approximately ⅓ ppm at 1.5 T. FIG. 13 shows that,with Gaussian amplitude modulation, the usable frequency range for areasonable uniform signal intensity is approximately double the usablefrequency range shown in FIG. 12. FIG. 14 shows that, with a sincfunction modulation, the usable frequency range for a reasonably uniformsignal intensity is approximately 30 Hz, or approximately 2 ppm, at 1.5T.

As shown in FIG. 14, imaging of a single hyperpolarized agent metaboliteshould be possible without additional shimming actions given that othermetabolites of interest are sufficiently far away from the excitedfrequency range. Further optimization of the excitation profiles shownin FIGS. 12-14 can be achieved by adjusting the modulation profile withthe respect to the position in the k-space, e.g., adjusting the maximumof the modulation profile such that it does not coincide with thepassage of the k-space center.

Referring now to FIG. 15, a hyperpolarized agent imaging technique 120in accordance with one embodiment of the present invention is shown. Thetechnique 120 begins with determining, at block 122, a low flip anglemodulation scheme for the RF pulse sequence of a modified trueFISP pulsesequence. Determination of the low flip angle modulation scheme includesbasing the determination on a desired frequency selectivity as describedabove as well as on the shimming, or the B₀ homogeneity. The low flipangle modulation scheme is based on a constant amplitude envelope, aGaussian modulation envelope, a sinc modulation envelope, or the like.Additionally, determination of the low flip angle modulation scheme mayinclude a consideration of the hyperpolarized contrast agent. In apreferred embodiment, the hyperpolarized contrast agent includes ¹³Cnuclei; however, it is contemplated that other hyperpolarized contrastagents may be used, such as ¹⁴N, ³¹P, ¹⁹F, and ²³Na nuclei, other NMRrelevant nuclei.

Following the determination at block 122 of the low flip anglemodulation scheme, an excitation profile of the modified trueFISP pulsesequence is adjusted at block 124 for excitation of a single metabolicspecies of the hyperpolarized contrast agent. For example, ahyperpolarized ¹³C-pyruvate may be injected into an imaging subject, andthe excitation profile may be adjusted to excite ¹³C-bicarbonate nuclei.The hyperpolarized contrast agent is then introduced into the imagingsubject at block 126. Next, the modified trueFISP pulse sequence excitesthe desired metabolic species at block 128. This excitation may bedelayed a specific time period after introduction of the agent to allowfor perfusion into tissues, or for the agent to reach an organ ofdiagnostic interest. Alternatively, a period of delay may correspond toan amount of time for the contrast agent to be metabolized. Signals arethen acquired from the excited metabolic species at block 130.

Technique 120 then determines at block 132 whether to excite a differentmetabolic species for acquiring signals therefrom. If so 134, then theexcitation profile is adjusted at block 136 to excite the nuclei foranother metabolite. The modulation scheme of the RF pulse sequence mayalso be adjusted, if desired, such that the modulation scheme for onemetabolite is distinct from the modulation scheme for anothermetabolite. Technique 120 then excites and acquires signals from theother metabolite as described above in blocks 128 and 130. If not 138,MR images are reconstructed for the acquired signal data at block 140.In a preferred embodiment, an image is reconstructed for each metaboliteacquired. However, it is contemplated that a combined image may bereconstructed for all metabolites acquired.

FIG. 16 shows an exemplary in vivo trueFISP image of a pig heart,acquired with a constant flip angle of 2°. Hyperpolarized ¹³C-pyruvatewas injected intravenously, and images were acquired with the excitationprofile adjusted to the resonance frequency of ¹³C-bicarbonate, which is160 Hz apart from the resonance frequency of pyruvate. FIG. 16 shows thesum of five consecutive images, acquired with 9-Hz frequency separationaround the bicarbonate resonance.

Therefore, in accordance with one embodiment of the present invention,an MRI apparatus includes an MRI assembly having a plurality of gradientcoils positioned about a bore of a magnet to impress a polarizingmagnetic field. An RF transceiver system and an RF switch are controlledby a pulse module to transmit and receive RF signals to and from an RFcoil assembly to acquire MR images. The MRI apparatus also includes asystem controller coupled to the MRI assembly, the system controllerconfigured to cause the RF coil assembly to excite a single metabolicspecies of a hyperpolarized agent injected into a subject of interest.The system controller further causes the RF transceiver system toacquire MR signals from the excited single metabolic species andreconstruct an image from the acquired MR signals.

In accordance with another embodiment of the invention, a method ofhyperpolarized agent MR imaging includes injecting a hyperpolarizedagent into a subject of interest and exciting a first metabolic speciesof the hyperpolarized agent. The method also includes acquiring MRsignals from the excited first metabolic species and reconstructing animage from the acquired MR signals.

According to a further embodiment of the invention, a computer readablestorage medium includes a computer program stored thereon comprisinginstructions which when executed by a computer, causes the computer tomodulate a plurality of flip angle train RF pulses of a pulse sequence.The instructions further cause the computer to acquire MR data from theplurality of molecules and generate an image from the MR data.

The present invention has been described in terms of the preferredembodiment, and it is recognized that equivalents, alternatives, andmodifications, aside from those expressly stated, are possible andwithin the scope of the appending claims.

What is claimed is:
 1. An MRI apparatus comprising: a magnetic resonanceimaging (MRI) assembly having a plurality of gradient coils positionedabout a bore of a magnet to impress a polarizing magnetic field and anRF transceiver system and an RF switch controlled by a pulse module totransmit RF signals to an RF coil assembly to acquire MR images; and asystem controller coupled to the MRI assembly, the system controllerconfigured to: cause the RF coil assembly to excite a single metabolicspecies of a hyperpolarized agent injected into a subject of interest;cause the RF transceiver system to acquire MR signals from the excitedsingle metabolic species; and reconstruct an image from the acquired MRsignals.
 2. The MRI apparatus of claim 1 wherein the excitation of thesingle metabolic species excites the single metabolic species only. 3.The MRI apparatus of claim 1 wherein the excited single metabolicspecies comprises a metabolite of the hyperpolarized agent injected intothe subject of interest.
 4. The MRI apparatus of claim 1 wherein thesystem controller is further configured to repeat the excitation and theacquisition for each single metabolic species of the hyperpolarizedagent.
 5. The MRI apparatus of claim 1 wherein the single metabolicspecies comprises a single metabolic species of 13C.
 6. A method ofhyperpolarized agent MR imaging comprising the steps of: injecting ahyperpolarized agent into a subject of interest; exciting only a firstmetabolic species of the hyperpolarized agent; acquiring MR signals fromthe excited first metabolic species; and reconstructing an image fromthe acquired MR signals.
 7. The method of claim 6 wherein the excitationof only the first metabolic species does not excite other metabolicspecies of the hyperpolarized agent.
 8. The method of claim 6 whereinthe excitation of the first metabolic species comprises a metabolite ofthe hyperpolarized agent injected into the subject of interest.
 9. Themethod of claim 6 wherein the step of exciting comprises: modifying aflip angle train according to a first low angle modulation pattern; andapplying a pulse sequence having the modified flip angle train to thefirst metabolic species.
 10. The method of claim 9 wherein the step ofmodifying comprises modifying the flip angle train according to aconstant amplitude low angle modulation pattern having amplitudes lessthan 2 degrees.
 11. The method of claim 9 wherein the step of modifyingcomprises modifying the flip angle train according to a Gaussianmodulated low angle modulation pattern.
 12. The method of claim 9wherein the step of modifying comprises modifying the flip angle trainaccording to a sinc function modulated low angle modulation pattern. 13.The method of claim 9 further comprising the steps of: exciting only asecond metabolic species of the hyperpolarized agent; and acquiring MRsignals from the excited second metabolic species.
 14. The method ofclaim 13 wherein the step of exciting the second metabolic speciescomprises: modifying the flip angle train according to a second lowangle modulation pattern distinct from the first low angle modulationpattern; and applying a pulse sequence having the modified flip angletrain according to the second low angle modulation pattern to the secondmetabolic species.
 15. A non-transitory computer readable storage mediumhaving stored thereon a computer program comprising instructions whichwhen executed by a computer, causes the computer to: modulate aplurality of flip angle train RF pulses of a pulse sequence; excite,with the pulse sequence, a plurality of molecules of a singlehyperpolarized metabolite within an object; acquire MR data from theplurality of molecules; and generate an image from the MR data.
 16. Thecomputer readable storage medium of claim 15 wherein the instructions,in exciting of the plurality of molecules of the single hyperpolarizedmetabolite with the pulse sequence, do not excite molecules of otherhyperpolarized metabolites within the object.